Global & Disaster Medicine

Archive for the ‘Nipah virus’ Category

Nipah in India: The first recorded NiV outbreak in South India.

J Infect Dis

Outbreak Investigation of Nipah Virus Disease in Kerala, India, 2018

The Journal of Infectious Diseases, jiy612, https://doi.org/10.1093/infdis/jiy612

“…..Results:  During 2–29 May 2018, 23 cases were identified, including the index case; 18 were laboratory confirmed. The lineage of the NiV responsible for this outbreak was closer to the Bangladesh lineage. The median age of cases was 45 years; the sex of 15 (65%) was male. The median incubation period was 9.5 days (range, 6–14 days). Of the 23 cases, 20 (87%) had respiratory symptoms. The case-fatality rate was 91%; 2 cases survived. Risk factors for infection included close proximity (ie, touching, feeding, or nursing a NiV-infected person), enabling exposure to droplet infection. The public health response included isolation of cases, contact tracing, and enforcement of hospital infection control practices.

Conclusion:  This is the first recorded NiV outbreak in South India…..”

CDC

Nipah virus (NiV) is a member of the family Paramyxoviridae, genus Henipavirus. NiV was initially isolated and identified in 1999 during an outbreak of encephalitis and respiratory illness among pig farmers and people with close contact with pigs in Malaysia and Singapore. Its name originated from Sungai Nipah, a village in the Malaysian Peninsula where pig farmers became ill with encephalitis. Given the relatedness of NiV to Hendra virus, bat species were quickly singled out for investigation and flying foxes of the genus Pteropus were subsequently identified as the reservoir for NiV….”

Distribution map showing areas endemic for Henipavirus Outbreaks and Pteropus.  Countries are Kuran, Tyumen, Omsk, and Novosibirsk

Transmission

bats flying in Bangladesh

Transmission of Nipah virus to humans may occur after direct contact with infected bats, infected pigs, or from other NiV infected people.

In Malaysia and Singapore, humans were apparently infected with Nipah virus only through close contact with infected pigs. The NiV strain identified in this outbreak appeared to have been transmitted initially from bats to pigs, with subsequent spread within pig populations. Incidental human infections resulted after exposure to infected pigs. No occurrence of person-to-person transmission was reported in this outbreak.

Conversely, person-to-person transmission of Nipah virus in Bangladesh and India is regularly reported. This is most commonly seen in the family and caregivers of Nipah virus-infected patients. Transmission also occurs from direct exposure to infected bats. A common example is consumption of raw date palm sap contaminated with infectious bat excretions.

Signs and Symptoms

Infection with Nipah virus is associated with encephalitis (inflammation of the brain). After exposure and an incubation period of 5 to 14 days, illness presents with 3-14 days of fever and headache, followed by drowsiness, disorientation and mental confusion. These signs and symptoms can progress to coma within 24-48 hours. Some patients have a respiratory illness during the early part of their infections, and half of the patients showing severe neurological signs showed also pulmonary signs.

During the Nipah virus disease outbreak in 1998-99, 265 patients were infected with the virus. About 40% of those patients who entered hospitals with serious nervous disease died from the illness.

Long-term sequelae following Nipah virus infection have been noted, including persistent convulsions and personality changes.

Latent infections with subsequent reactivation of Nipah virus and death have also been reported months and even years after exposure.

Treatment

Treatment is limited to supportive care. Because Nipah virus encephalitis can be transmitted person-to-person, standard infection control practices and proper barrier nursing techniques are important in preventing hospital-acquired infections (nosocomial transmission).

The drug ribavirin has been shown to be effective against the viruses in vitro, but human investigations to date have been inconclusive and the clinical usefulness of ribavirin remains uncertain.

Passive immunization using a human monoclonal antibody targeting the Nipah G glycoprotein has been evaluated in the post-exposure therapy in the ferret model and found to be of benefit.

 


WHO: Prioritizing Emerging Infectious Diseases in Need of Research and Development

The World Health Organization R&D Blueprint aims to accelerate the availability of medical technologies during epidemics by focusing on a list of prioritized emerging diseases for which medical countermeasures are insufficient or nonexistent. The prioritization process has 3 components: a Delphi process to narrow down a list of potential priority diseases, a multicriteria decision analysis to rank the short list of diseases, and a final Delphi round to arrive at a final list of 10 diseases.

A group of international experts applied this process in January 2017, resulting in a list of 10 priority diseases. The robustness of the list was tested by performing a sensitivity analysis. The new process corrected major shortcomings in the pre–R&D Blueprint approach to disease prioritization and increased confidence in the results.

Multicriteria scores of diseases considered in the 2017 prioritization exercise for the development of the World Health Organization R&D Blueprint to prioritize emerging infectious diseases in need of research and development. A) Disease final ranking using the geometric average of the comparison matrices. B) Disease final ranking using the arithmetic average of the raw data. Error bars correspond to SD, indicating disagreement among experts. C) Disease final ranking using the SMART Vaccines

Multicriteria scores of diseases considered in the 2017 prioritization exercise for the development of the World Health Organization R&D Blueprint to prioritize emerging infectious diseases in need of research and development. A) Disease final ranking using the geometric average of the comparison matrices. B) Disease final ranking using the arithmetic average of the raw data. Error bars correspond to SD, indicating disagreement among experts. C) Disease final ranking using the SMART Vaccines prioritization tool (56). P1, Ebola virus infection; P2, Marburg virus infection; P3, Middle East Respiratory Syndrome coronavirus infection; P4, severe acute respiratory syndrome; P5, Lassa virus infection; P6, Nipah virus infection; P7, Rift Valley fever; P8, Zika virus infection; P9, Crimean-Congo hemorrhagic fever; P10, severe fever with thrombocytopenia syndrome; P11, South American hemorrhagic fever; P12, plague; P13, hantavirus infection.

Si Mehand M, Millett P, Al-Shorbaji F, Roth C, Kieny MP, Murgue B. World Health Organization methodology to prioritize emerging infectious diseases in need of research and development. Emerg Infect Dis. 2018 Sep [date cited]. https://doi.org/10.3201/eid2409.171427


Nipah virus – India: WHO officially declares India’s 19-case Nipah outbreak over

WHO

 Groundwater Gains in India

Disease outbreak news
7 August 2018

As of 17 July 2018, a total of 19 Nipah virus (NiV) cases, including 17 deaths, were reported from Kerala State: 18 of the cases were laboratory-confirmed and the deceased index case was suspected to have NiV but could not be tested. The outbreak was localized to two districts in Kerala State: Kozhikode and Malappuram. No new cases or deaths have been reported since 1 June 2018 and, as of 30 July, human-to-human transmission of NiV has been contained in Kerala State.

As reported in the Disease Outbreak News published on 31 May 2018, three deaths due to NiV infection were reported on 19 May from Kozhikode District, Kerala State. Three of the four reported deaths were confirmed positive for NiV by real-time polymerase chain reaction (RT-PCR) and IgM ELISA for NiV.

Two patients recovered completely and were discharged from the hospital. Acute respiratory distress syndrome and encephalitis were observed among the patients infected. This was the first NiV outbreak reported in Kerala State and the third NiV outbreak known to have occurred in India; the two previous outbreaks occurred in the state of West Bengal in 2001 and 2007.

Public health response

Government response

  • A multi-disciplinary central team from the National Centre for Disease Control was sent to Kerala to investigate and respond, in close coordination with state government officials.
  • More than 2600 contacts were identified and followed up during the outbreak. All symptomatic contacts were investigated and tested for NiV.
  • Syndromic surveillance was enhanced in Kerala State. Hospital and community surveillance were also strengthened in Kerala. The Virus Research Diagnostic Laboratory at Manipal Hospital and the National Institute of Virology conducted laboratory testing to confirm and rule out cases.
  • The central team provided Kerala officials with the following guidelines and reference materials for Nipah virus, which were made publically available during the outbreak: case definitions; guidelines for hospital infection prevention and control; guidelines for sample collection and transportation; clinical management guidelines for suspected and confirmed cases; guidelines for safe disposal of dead bodies of confirmed Nipah virus cases; and information for the general public and for health care personnel. Risk communication messages were delivered to the community, public, partners and other stakeholders.
  • Training and capacity building for health care personnel were done in the following areas: sample collection and transportation; safe disposal of dead bodies; contact tracing; hospital waste management; hospital infection prevention and control; and the use of personal protective equipment.
  • The government coordinated amongst all relevant sectors including zoonoses, wildlife, animal husbandry, human health, clinicians, pulmonologists, neurologists and private sector.
  • The Strategic Health Operations Centre (SHOC) at the National Centre for Disease Control was activated to monitor the outbreak.
  • The Ministry of Health provided the Kerala government with 5000 personal protective equipment kits and 100 body bags.
  • Samples from animals (bats, pigs, cows, and goats) tested at National High Security Animal Diseases Laboratory at Bhopal early in the outbreak tested negative for NiV. Later, Pteropus giganteus bats (the reservoir of NiV infection) were collected from areas around the house of the index case in Kozhikode, Kerala to understand the circulation of NiV in bats in the affected area; 19% (10 of 52) of the bats were found positive by RT-PCR for NiV.

WHO response

  • As per the International Health Regulations (IHR 2005), the event was notified to WHO on 23 May 2018 and WHO published a Disease Outbreak News on 31 May 2018.
  • WHO provided technical materials and guidance on Nipah virus disease to the Ministry of Health and Kerala State health authorities, and provided technical support to the Ministry of Health.
  • WHO continues to work closely with the Ministry of Health to strengthen overall indicator- and event-based surveillance for epidemic-prone diseases and strengthen overall IHR (2005) capacities.
  • WHO is also working with the Indian Council of Medical Research (ICMR) to advance the research agenda for the Nipah research and development (R&D) blueprint. WHO will continue working closely with the Ministry of Health to ensure that health systems preparedness for emerging zoonoses is strengthened in the country.

WHO risk assessment

NiV infection is an emerging zoonotic disease of public health importance in the WHO South-East Asia Region with a high case fatality rate estimated to range between 40 and 75%; however, this rate can vary by outbreak depending on local capabilities for epidemiological surveillance and clinical management. NiV was first recognized in 1998-1999 during an outbreak among pig farmers in Malaysia and Singapore. No subsequent outbreaks have been reported in Malaysia or Singapore since 1999. NiV was first recognized in India and Bangladesh in 2001; since then, nearly annual outbreaks have occurred in Bangladesh. The disease has been identified periodically in eastern India (2001, 2007).

Limited human-to-human transmission of NiV can occur among unprotected family members and health workers who treat infected patients. Fruit bats of the genus Pteropus are the natural reservoirs of NiV. Possible routes of transmission of NiV include consumption of fruit contaminated by the saliva of infected bats, from direct contact with infected bats or their feces/urine, or human-to-human transmission through unprotected close contact with an infected patient in the community or hospital. Many cases identified in the current outbreak were infected through direct unprotected contact with other infected persons.

This outbreak is the third Nipah virus outbreak in India. The country demonstrated its capacity to rapidly contain the outbreak, including by the identification of cases, verifying cases with laboratory testing and caring for patients.

WHO advice

Currently, there is no evidence of NiV infection in humans in Kerala State; however, surveillance for NiV in humans and fruit bats should be maintained in endemic areas.

WHO advises against the application of any travel or trade restrictions on India based on the information currently available on this event.

Currently, there are no specific treatments available for Nipah virus disease and care is supportive. Intensive supportive care is recommended to treat severe respiratory and neurologic complications.

NiV infection can be prevented by avoiding exposure to bats and sick pigs in endemic areas, and by avoiding consuming fruits partially-eaten by infected bats or drinking raw date palm sap/toddy/juice. The risk of international transmission via fruit contaminated with urine or saliva from infected fruit bats can be prevented by washing them thoroughly and peeling them before consumption. Fruit with signs of bat bites should be discarded.

In health care settings, staff should consistently implement standard infection prevention and control measures when caring for patients to prevent nosocomial infections. Health care workers caring for a patient suspected to have NiV fever should immediately contact local and national experts for guidance and to arrange for laboratory testing.

Research is needed to better understand the ecology of bats and NiV.


India: 17 of the 19 infected people might have contracted the Nipah virus from the first victim

Deccan Chronicle

“…..Mohammed Sabith first took treatment as an ‘out patient’ at the Perambra hospital for high fever and body pain on May 2.

On May 3, he was admitted at the hospital, and it is suspected that four people on night duty including sister Lini Puthussery, who attended to him, picked the virus from him.

As his condition worsened on May 4, Mohammed Sabith was shifted to the Medical College hospital for a CT scan, where he died on May 5. Ten people got infected at the medical college on the single day he was there….”

Distribution map showing areas endemic for Henipavirus Outbreaks and Pteropus.  Countries are Kuran, Tyumen, Omsk, and Novosibirsk


Can Nipah virus lead to another pandemic?

Lancet

“……Evidence from Bangladesh shows that viral spillovers from bats to humans happen regularly, providing an opportunity for a more highly transmissible strain to infect and adapt in humans. Fuelled by population density and mobility, such evolution increases the risk of a pandemic…..”

Distribution map showing areas endemic for Henipavirus Outbreaks and Pteropus. Countries are Kuran, Tyumen, Omsk, and Novosibirsk


India: One more person confirmed to have contracted the Nipah Virus infection passed away in Kerala, taking the death toll to 17.

TNM

“……Suspecting a second wave of the infection, the authorities have scaled up the number of people, who are under observation for Nipah Virus to 1407.

Meanwhile, the medicines from Australia to fight the Nipah Virus – M 102.4 human monoclonal antibody arrived in Kozhikode on Thursday night and will be administered to patients as per the treatment protocol. ……”

 


Nipah virus update – India

WHO

Disease Outbreak News
31 May 2018

On 19 May 2018, three deaths due to Nipah virus infection were reported in Kozhikode District, Kerala State, India. The three deaths occurred in a family cluster and a fourth death was subsequently reported in a health care worker who was involved in treatment of the family in the local hospital. Laboratory testing of throat swabs, urine and blood samples collected from four suspected patients has been conducted by the National Institute of Virology in Pune; three of the four reported deaths were confirmed positive for Nipah virus (NiV) by real-time polymerase chain reaction (RT-PCR) and IgM Elisa for NiV.

The field investigation team found bats living in the abandoned water well on the premises of a new house where the family had plans to move after renovation. One bat was caught and sent to the National Institute of Virology, Pune for laboratory testing.

As of 28 May 2018 and since the beginning of the outbreak, as a result of further investigations and contact tracing, 15 people have tested positive for NiV in Kozhikode and Malappuram districts, Kerala State. Of the 15 laboratory-confirmed cases, two are hospitalized and thirteen have died, including the health care worker who was involved in treatment of the deceased. As of 28 May, 13 deaths have been reported: three from Malappuram District and ten from Kozhikode District. One deceased case, the index case, could not be tested but was epidemiologically linked to a confirmed case. There are 16 suspected cases identified through contact tracing who are under observation while their laboratory results are pending and at least 753 additional people, including health care workers, under observation. Laboratory testing is being conducted by the Manipal Institute of Virus Research and the National Institute of Virology, Pune; both laboratories have advanced capacity for RT-PCR.

In the current outbreak, acute respiratory distress syndrome and encephalitis have been observed.

This is the first NiV outbreak reported in Kerala State and third NiV outbreak known to have occurred in India, with the most recent outbreak reported in 2007.

Public health response

Government response

  • A multi-disciplinary central team from the National Centre for Disease Control was sent to Kerala to investigate and respond. Contact tracing has been initiated. Infection prevention and control measures have been strengthened in health facilities.
  • Acute fever and acute encephalitis syndrome (AES) surveillance have been enhanced across the state. Hospital and community surveillance have also been strengthened in Kerala.
  • The Virus Research Diagnostic Laboratory at Manipal Hospital and the National Institute of Virology are conducting laboratory testing to confirm cases.
  • The government is coordinating with all relevant sectors including zoonosis, wildlife, animal husbandry, human health, clinicians, pulmonologists, neurologists and private sector.
  • Risk communication messages are being delivered to the community, public, stakeholders, and partners. The Ministry of Health and Family Welfare (MoHFW) has shared guidelines drafted by the National Centre for Disease Control with states and relevant stakeholders and also posted them on the MoHFW website.

WHO response

  • WHO is in contact with national authorities and continues to closely monitor this event.
  • At the request of the MoHFW, WHO has shared materials, especially risk communication materials on Nipah virus, including those used in Bangladesh.
  • The MoHFW is conducting preliminary investigations and may request that WHO support the response.
  • The MoHFW is coordinating a multi-dimensional investigation and may request support from WHO.

WHO risk assessment

NiV infection is an emerging zoonotic disease of public health importance in the WHO South-East Asia Region with a high case fatality rate estimated to be between 40 and 75%; however, this rate can vary by outbreak depending on local capabilities for epidemiological surveillance and clinical management. NiV was first recognized in 1998-1999 during an outbreak among pig farmers in Malaysia and Singapore. No subsequent outbreaks have been reported in Malaysia or Singapore since 1999. NiV was first recognized in India and Bangladesh in 2001; since then, nearly annual outbreaks have occurred in Bangladesh. The disease has been identified periodically in eastern India (2001, 2007).

Limited human-to-human transmission of NiV can occur among family members and health workers who treat infected patients. Large fruit bats of the genus Pteropus are the natural reservoirs of NiV and given the wide distribution of the species and migration of the locally-abundant fruit bats in India, the risk of exposure to NiV is high. Nevertheless, previous outbreaks in affected countries have had a strong seasonal pattern and a limited geographical range.

Possible routes of transmission for this outbreak include consumption of fruits partially eaten by the bats, exposure to the virus by bats or human-to-human transmission through unprotected close contact in the community or hospital. Many cases identified in the current outbreak were infected through direct unprotected contact with other infected persons.

Given that India has faced and contained Nipah virus outbreaks before, the country has the capacity to rapidly respond and verify cases with laboratory testing. At the moment, the outbreak is localized and WHO assesses the risk to be low at the national and regional levels.

WHO advice

Currently, there are no specific treatments available for Nipah virus disease and care is supportive. Intensive supportive care is recommended to treat severe respiratory and neurologic complications.

NiV infection can be prevented by avoiding exposure to sick pigs and bats in endemic areas, and by avoiding consuming fruits partially-eaten by infected bats or drinking raw date palm sap/toddy/juice.

In health care settings, staff should consistently implement standard infection prevention and control measures when caring for patients to prevent nosocomial infections. Health care workers caring for a patient suspected to have NiV fever should immediately contact local and national experts for guidance and to arrange for laboratory testing.

Research is needed to better understand the ecology of bats and NiV.

WHO advises against the application of any travel or trade restrictions on India based on the information currently available on this event.


NiV in India: As of May 24, 34 cases have been reported, 14 of them confirmed and 20 suspected. So far 12 deaths have been reported in two Kerala districts, Kozhikode and Malappuram.

WHO

Ministry of Health and Family Welfare
Central High-level Team: Nipah virus disease is not a major outbreak. It is only a local occurrence.

Following directions of the Union Health Minister, Shri J P Nadda, a multi-disciplinary Central Team led by the National Centre for Disease Control (NCDC) is presently in Kerala constantly reviewing the situation of the Nipah Virus Disease. After reviewing the cases of all the patients who have lost their lives, the Central High-level Team is of the view that the Nipah virus disease is not a major outbreak and is only a local occurrence. The Team has also further fine-tuned the draft guidelines, case definitions, advisory for healthcare workers, information to the general public, advisories for sample collection and transportation accordingly. The Central Team held meetings with the District Collectors and the medical and para-medical staff of the hospitals today also to review the condition of the admitted patients and to consider further course of action to be taken to prevent the disease from spreading. The efforts taken so far for containment of the disease have been fruitful as the disease has not spread to new areas. The contact tracing strategy adopted has also been successful. It has been found that all the reported cases including the suspected cases had direct or indirect contact with the first casualty/his family prior to contacting the disease. General awareness among the general public has been encouraging. They have been asked to follow safe hygiene practices, not to consume fruits/vegetables partly eaten by birds/animals and steps to be taken while going near the infected persons/areas. The State Government has also issued advisories in the vernacular. The continued round-the-clock presence of the Central and State Teams in the affected areas right from day one of the outbreak and the surveillance and preventive actions taken by them, have instilled confidence among the public. The Team also reviewed/discussed with the hospitals the management and treatment of the patients. The treatment procedure adopted by the hospitals for the patients with specific/non-specific symptoms has been found effective. The suspect cases admitted in the Kozhikode Medical College and Trivandrum Medical College are under observation. All healthcare workers have adopted safe practices for dealing with the patients. The Union Minister for Health and Family Welfare is closely monitoring the situation. Details of cases and deaths, as on 24.5.2018, are as under: Total number of confirmed cases: 14 Total number of suspected cases: 20 Total number of deaths: 12 (9 from Kozhikode and 3 from Malappuram)

(Release ID: 1533423)


CDC on NiV (Nipah virus)

CDC

Nipah virus (NiV) is a member of the family Paramyxoviridae, genus Henipavirus. NiV was initially isolated and identified in 1999 during an outbreak of encephalitis and respiratory illness among pig farmers and people with close contact with pigs in Malaysia and Singapore. Its name originated from Sungai Nipah, a village in the Malaysian Peninsula where pig farmers became ill with encephalitis. Given the relatedness of NiV to Hendra virus, bat species were quickly singled out for investigation and flying foxes of the genus Pteropus were subsequently identified as the reservoir for NiV (Distribution Map).

In the 1999 outbreak, Nipah virus caused a relatively mild disease in pigs, but nearly 300 human cases with over 100 deaths were reported. In order to stop the outbreak, more than a million pigs were euthanized, causing tremendous trade loss for Malaysia. Since this outbreak, no subsequent cases (in neither swine nor human) have been reported in either Malaysia or Singapore.

In 2001, NiV was again identified as the causative agent in an outbreak of human disease occurring in Bangladesh. Genetic sequencing confirmed this virus as Nipah virus, but a strain different from the one identified in 1999. In the same year, another outbreak was identified retrospectively in Siliguri, India with reports of person-to-person transmission in hospital settings (nosocomial transmission). Unlike the Malaysian NiV outbreak, outbreaks occur almost annually in Bangladesh and have been reported several times in India.

Transmission

bats flying in Bangladesh

Transmission of Nipah virus to humans may occur after direct contact with infected bats, infected pigs, or from other NiV infected people.

In Malaysia and Singapore, humans were apparently infected with Nipah virus only through close contact with infected pigs. The NiV strain identified in this outbreak appeared to have been transmitted initially from bats to pigs, with subsequent spread within pig populations. Incidental human infections resulted after exposure to infected pigs. No occurrence of person-to-person transmission was reported in this outbreak.

Conversely, person-to-person transmission of Nipah virus in Bangladesh and India is regularly reported. This is most commonly seen in the family and caregivers of Nipah virus-infected patients. Transmission also occurs from direct exposure to infected bats. A common example is consumption of raw date palm sap contaminated with infectious bat excretions.

Signs and Symptoms

Infection with Nipah virus is associated with encephalitis (inflammation of the brain). After exposure and an incubation period of 5 to 14 days,illness presents with 3-14 days of fever and headache, followed by drowsiness, disorientation and mental confusion. These signs and symptoms can progress to coma within 24-48 hours. Some patients have a respiratory illness during the early part of their infections, and half of the patients showing severe neurological signs showed also pulmonary signs.

During the Nipah virus disease outbreak in 1998-99, 265 patients were infected with the virus. About 40% of those patients who entered hospitals with serious nervous disease died from the illness.

Long-term sequelae following Nipah virus infection have been noted, including persistent convulsions and personality changes.

Latent infections with subsequent reactivation of Nipah virus and death have also been reported months and even years after exposure.

Risk of Exposure

clay pot with raw date palm sap inside, credit to Ilana Schafer

In the Malaysia and Singapore outbreak, Nipah virus infection was associated with close contact with Nipah virus-infected pigs.

In Bangladesh and India, where Nipah virus infection is more frequent, exposure has been linked to consumption of raw date palm sap and contact with bats. Importantly, human-to-human transmission has been documented and exposure to other Nipah virus infected individuals is also a risk factor.

Diagnosis

Nipah virus infection in human central nervous system tissue specimen, credit to CDC PHIL

Laboratory diagnosis of a patient with a clinical history of NiV can be made during the acute and convalescent phases of the disease by using a combination of tests. Virus isolation attempts and real time polymerase chain reaction (RT-PCR) from throat and nasal swabs, cerebrospinal fluid, urine, and blood should be performed in the early stages of disease. Antibody detection by ELISA (IgG and IgM) can be used later on. In fatal cases, immunohistochemistry on tissues collected during autopsy may be the only way to confirm a diagnosis.

Treatment

Treatment is limited to supportive care. Because Nipah virus encephalitis can be transmitted person-to-person, standard infection control practices and proper barrier nursing techniques are important in preventing hospital-acquired infections (nosocomial transmission).

The drug ribavirin has been shown to be effective against the viruses in vitro, but human investigations to date have been inconclusive and the clinical usefulness of ribavirin remains uncertain.

Passive immunization using a human monoclonal antibody targeting the Nipah G glycoprotein has been evaluated in the post-exposure therapy in the ferret model and found to be of benefit.

Prevention

hospital poster credit to Ilana Schafer

Nipah virus infection can be prevented by avoiding exposure to sick pigs and bats in endemic areas and not drinking raw date palm sap.

Additional efforts focused on surveillance and awareness will help prevent future outbreaks. Research is needed to better understand the ecology of bats and Nipah virus, investigating questions such as the seasonality of disease within reproductive cycles of bats. Surveillance tools should include reliable laboratory assays for early detection of disease in communities and livestock, and raising awareness of transmission and symptoms is important in reinforcing standard infection control practices to avoid human-to-human infections in hospital settings (nosocomial infection).

A subunit vaccine, using the Hendra G protein, produces cross-protective antibodies against HENV and NIPV has been recently used in Australia to protect horses against Hendra virus. This vaccine offers great potential for henipavirus protection in humans as well.

Distribution map showing areas endemic for Henipavirus Outbreaks and Pteropus. Countries are Kuran, Tyumen, Omsk, and Novosibirsk

References

  • MMWR, Outbreak of Hendra-like virus—Malaysia and Singapore, 1998-1999. Apr 9, 1999;48(3):265-9.
  • MMWR, Update: Outbreak of Nipah virus– Malaysia and Singapore, 1999. Apr 30, 1999;48(16):335-7.
  • Broder CC. Henipavirus outbreaks to antivirals: the current status of potential therapeutics. Current Opinion Virology 2012;2(2):176-87.
  • Chadha MS, Comer JA, Lowe L, et al. Nipah virus-associated encephalitis outbreak, Siliguri, India. Emerging Infectious Disease 2006;12(2):235-40.
  • Chua KB, Goh KJ, Wong KT, et al. Fatal encephalitis due to Nipah virus among pig-farmers in Malaysia. Lancet 1999;354(9186):1257-9.
  • Chua KB, Bellini WJ, Rota PA, et al. Nipah virus: A recently emergent deadly paramyxovirus. Science 2000;288(5470):1432-5.
  • Chua KB, Lam SK, Goh KJ, et al. The presence of Nipah virus in respiratory secretions and urine of patients during an outbreak of Nipah virus encephalitis in Malaysia. Journal of Infection 2001;42(1):40-3.
  • Daniels P, Ksiazek T, Eaton BT. Laboratory diagnosis of Nipah and Hendra virus infections. Microbes and Infection 2001;3(4):289-95.
  • Field HE, Mackenzie JS, Daszak P. Henipaviruses: emerging paramyxoviruses associated with fruit bats. Current Topics Microbiology and Immunology 2007;315:133-59.
  • Gurley ES, Montgomery JM, Hossain MJ, et al. Person-to-person transmission of Nipah virus in a Bangladeshi community. Emerging Infectious Disease 2007;13(7):1031-7.
  • Hossain MJ, Gurley ES, Montgomery JM, et al. Clinical presentation of Nipah virus infection in Bangladesh. Clinical Infectious Diseases 2008;46(7):977-84.
  • Lee KE, Umapathi T, Tan CB, et al. The neurological manifestations of Nipah virus encephalitis, a novel paramyxovirus. Annals of Neurology 1999;46428-32.
  • Lim CCT, Lee KE, Lee WL, et al. Nipah virus encephalitis: Serial MR study of an emerging disease. Radiology 2002;222(1):219-26.
  • Luby SP, Gurley ES, Hossain MJ. Transmission of human infection with Nipah virus. Clinical Infectious Disease 2009;49(11):1743-8.
  • Mounts AW, Kaur H, Parashar UD, et al. A cohort study of health care workers to assess nosocomial transmissibility of Nipah virus, Malaysia, 1999. Journal of Infectious Disease 2001;183(5):810-3.
  • Murray K, Selleck P, Hooper P, et al. A morbillivirus that caused fatal disease in horses and humans. Science 1995;268:94-7.
  • Paton NI, Leo YS, Zaki SR, et al. Outbreak of Nipah-virus infection among abattoir workers in Singapore. Lancet 1999;354(9186):1253-6.
  • Rahman MA, Hossain MJ, Sultana S, et al. Date Palm Sap Linked to Nipah Virus Outbreak in Bangladesh, 2008. Vector-Borne and Zoonotic Disease 2012;12(1):65-73.
  • Reynes J-M, Counor D, Ong S, et al. Nipah virus in Lyle’s Flying Foxes, Cambodia. Emerging Infectious Disease 2005;11(7):1042-7.
  • Rollin PE, Rota P, Zaki S, Ksiazek TG. Hendra and Nipah viruses. in: Versalovic J, Carroll KC, Funke G, Jorgensen JH, Landry ML, Warnock DW, editors. Manual of Clinical Microbiology. 10th ed. Washington, DC: ASM Press; 2011; p. 1479-87.
  • Sim BF, Jusoh MR, Chang CC, Khalid R. Nipah Encephalitis: A report of 18 patients from Kuala Lumpur Hospital. Neurology Journal Southeast Asia 2002;7:13-8.
  • Tan CT, Goh KJ, Wong KT, et al. Relapsed and Late-Onset Nipah Encephalitis. Ann. Neurology 2002;51(6):703-8.
  • Wacharapluesadee S, Boongird K, Wanghongsa S, et al. A Longitudinal Study of the Prevalence of Nipah Virus in Pteropus lylei Bats in Thailand: Evidence for Seasonal Preference in Disease Transmission. Vector-Borne and Zoonotic Disease 2010;10(2):183-90.
  • Williamson M, Torres-Velez FJ. Henipavirus: a review of laboratory animal pathology. Veterinary Pathology 2010;47(5):871-80.
  • Wong KT, Shieh WJ, Kumar S, et al. Nipah virus infection. Pathology and pathogenesis of an emerging paramyxoviral zoonosis. American Journal of Pathology 2002;161(6):2153-67.

WHO: NiV update and review

 

WHO

Nipah virus

22 May 2018
 

Key facts

  • Nipah virus is an RNA virus that is part of the Paramyxovidae family that was first identified as a zoonotic pathogen after an outbreak involving severe respiratory illness in pigs and encephalitic disease in humans in Malaysia and Singapore in 1998 and 1999.
  • Nipah virus can cause a range of mild to severe disease in domestic animals such as pigs.
  • Nipah virus infection in humans causes a range of clinical presentations, from asymptomatic infection (subclinical) to acute respiratory infection and fatal encephalitis.
  • Nipah virus can be transmitted to humans from animals (bats, pigs), and can also be transmitted directly from human-to-human.
  • Fruit bats of the Pteropodidae family are the natural host of Nipah virus.
  • There is no treatment or vaccine available for either people or animals. The primary treatment for humans is supportive care.
  • Nipah virus is on the WHO list of Blueprint priority diseases

Nipah virus (NiV) is an emerging zoonotic virus (a virus transmitted to humans from animals). In infected people, Nipah virus causes a range of illnesses from asymptomatic (subclinical) infection to acute respiratory illness and fatal encephalitis. NiV can also cause severe disease in animals such as pigs, resulting in significant economic losses for farmers.

Nipah virus is closely related to Hendra virus. Both are members of the genus Henipavirus, a new class of virus in the Paramyxoviridae family.

Although Nipah virus has caused only a few outbreaks, it infects a wide range of animals and causes severe disease and death in people, making it a public health concern.

Past Outbreaks

Nipah virus was first recognized in 1999 during an outbreak among pig farmers in Kampung Sungai Nipah, Malaysia. No new outbreaks have been reported in Malaysia and Singapore since 1999.

NiV was first recognized in Bangladesh in 2001 and nearly annual outbreaks have occurred in that country since, with disease also identified periodically in eastern India.

Other regions may be at risk for NiV infection, as serologic evidence for NiV has been found in the known natural reservoir (Pteropus bat species) and several other bat species in a number of countries, including Cambodia, Thailand, Indonesia, Madagascar, Ghana and the Philippines.

Transmission

NiV is a zoonotic virus (a virus transmitted to humans from animals). During the initial outbreaks in Malaysia and Singapore, most human infections resulted from direct contact with sick pigs or their contaminated tissues. Transmission is thought to have occurred via respiratory droplets, contact with throat or nasal secretions from the pigs, or contact with the tissue of a sick animal.

In the Bangladesh and India outbreaks, consumption of fruits or fruit products (e.g. raw date palm juice) contaminated with urine or saliva from infected fruit bats was the most likely source of infection.

Limited human to human transmission of NiV has also been reported among family and care givers of infected NiV patients. During the later outbreaks in Bangladesh and India, Nipah virus spread directly from human-to-human through close contact with people’s secretions and excretions. In Siliguri, India, transmission of the virus was also reported within a health-care setting (nosocomial), where 75% of cases occurred among hospital staff or visitors. From 2001 to 2008, around half of reported cases in Bangladesh were due to human-to-human transmission through providing care to infected patients.

Signs and symptoms

Human infections range from asymptomatic infection, acute respiratory infection (mild, severe), and fatal encephalitis. Infected people initially develop influenza-like symptoms of fever, headaches, myalgia (muscle pain), vomiting and sore throat. This can be followed by dizziness, drowsiness, altered consciousness, and neurological signs that indicate acute encephalitis. Some people can also experience atypical pneumonia and severe respiratory problems, including acute respiratory distress. Encephalitis and seizures occur in severe cases, progressing to coma within 24 to 48 hours.

The incubation period (interval from infection to the onset of symptoms) is believed to range between from 4-14 days. However an incubation period as long as 45 days has been reported.

Most people who survive acute encephalitis make a full recovery, but long term neurologic conditions have been reported in survivors.  Approximately 20% of patients are left with residual neurological consequences such as seizure disorder and personality changes. A small number of people who recover subsequently relapse or develop delayed onset encephalitis.

The case fatality rate is estimated at 40% to 75%; however, this rate can vary by outbreak depending on local capabilities for epidemiological surveillance and clinical management.

Diagnosis

Initial signs and symptoms of NiV infection are non-specific and the diagnosis is often not suspected at the time of presentation.  This can hinder accurate diagnosis and creates challenges in outbreak detection and institution of effective and timely infection control measures and outbreak response activities.

In addition, clinical sample quality, quantity, type, timing of collection and the time necessary to transfer samples from patients to the laboratory can affect the accuracy of laboratory results.

NiV infection can be diagnosed together with clinical history during the acute and convalescent phase of the disease. Main tests including real time polymerase chain reaction (RT-PCR) from bodily fluids as well as antibody detection via ELISA.  Different tests include:

  • enzyme-linked immunosorbent assay (ELISA)
  • polymerase chain reaction (PCR) assay
  • ·virus isolation by cell culture.

Treatment

There are currently no drugs or vaccines specific for NiV infection although this is a priority disease on the WHO R&D Blueprint.  Intensive supportive care is recommended to treat severe respiratory and neurologic complications.

Natural host: fruit bats

Fruit bats of the family Pteropodidae – particularly species belonging to the Pteropus genus – are the natural hosts for Nipah virus. There is no apparent disease in fruit bats.

It is assumed that the geographic distribution of Henipaviruses overlaps with that of Pteropus category. This hypothesis was reinforced with the evidence of Henipavirus infection in Pteropus bats from Australia, Bangladesh, Cambodia, China, India, Indonesia, Madagascar, Malaysia, Papua New Guinea, Thailand and Timor-Leste.

African fruit bats of the genus Eidolon, family Pteropodidae, were found positive for antibodies against Nipah and Hendra viruses, indicating that these viruses might be present within the geographic distribution of Pteropodidae bats in Africa.

Nipah virus in domestic animals

Nipah outbreaks in pigs and other domestic animals (horses, goats, sheep, cats and dogs) were first reported during the initial Malaysian outbreak in 1999.

Nipah virus is highly contagious in pigs. Pigs are infectious during the incubation period, which lasts from 4 to 14 days.

An infected pig can exhibit no symptoms, but some develop acute feverish illness, labored breathing, and neurological symptoms such as trembling, twitching and muscle spasms. Generally, mortality was low except in young piglets. These symptoms are not dramatically different from other respiratory and neurological illnesses of pigs. Nipah should be suspected if pigs also have an unusual barking cough or if human cases of encephalitis are present.

Prevention

Controlling Nipah virus in domestic animals

 

Currently, there are no vaccines available against Nipah virus. Routine and thorough cleaning and disinfection of pig farms (with appropriate detergents) may be effective in preventing infection.

If an outbreak is suspected, the animal premises should be quarantined immediately.  Culling of infected animals – with close supervision of burial or incineration of carcasses – may be necessary to reduce the risk of transmission to people. Restricting or banning the movement of animals from infected farms to other areas can reduce the spread of the disease.

As Nipah virus outbreaks in domestic animals have preceded human cases, establishing an animal health surveillance system, using a One Health approach, to detect new cases is essential in providing early warning for veterinary and human public health authorities.

Reducing the risk of infection in people

In the absence of a licensed vaccine, the only way to reduce infection in people is by raising awareness of the risk factors and educating people about the measures they can take to reduce exposure to and decrease infection from NiV.

Public health educational messages should focus on the following:

 

  • Reducing the risk of bat-to-human transmission: Efforts to prevent transmission should first focus on decreasing bat access to date palm sap and to other fresh food products. Keeping bats away from sap collection sites with protective coverings (e.g., bamboo sap skirts) may be helpful.Freshly collected date palm juice should be boiled and fruits should be thoroughly washed and peeled before consumption.
  • Reducing the risk of animal-to-human transmission: Gloves and other protective clothing should be worn while handling sick animals or their tissues, and during slaughtering and culling procedures. As much as possible, people should avoid being in contact with infected pigs.
  • Reducing the risk of human-to-human transmission: Close unprotected physical contact with Nipah virus-infected people should be avoided. Regular hand washing should be carried out after caring for or visiting sick people.

Controlling infection in health-care settings

  • Health-care workers caring for patients with suspected or confirmed NiV infection, or handling specimens from them, should implement standard infection control precautions for all patients at all times
  • As human-to-human transmission in particular nosocomial transmission have been reported, contact and droplet precautions should be used in addition to standard precautions.
  • Samples taken from people and animals with suspected NiV infection should be handled by trained staff working in suitably equipped laboratories.

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